Dehydroepiandrosterone Sulfate Level Varies Nonlinearly with Symptom Severity in Major Depressive Disorder

Objective: The pathophysiology of major depressive disorder (MDD) is still not well understood. Conflicting results for surrogate biomarkers in MDD have been reported, which might be a consequence of the heterogeneity of MDD patients. Therefore, we aim to investigate how the severity of depression and various symptom domains are related to the levels of dehydroepiandroster-one sulfate (DHEA-s) in MDD patients. Methods: We recruited 117 subjects from a general practice. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Depressive symptoms were divided into three subdomains according to BDI items; somatic symptoms, guilt and failure, and mood and inhibition. Results: In subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI score did. However, the DHEA-s levels in the subjects with severe depression were significantly lower than in subjects with moderate depression ( p =0.003). DHEA-s level was correlated with the BDI subscore for guilt and failure in very-mild-to-moderate depression (r=0.365, p =0.006). Conclusion: The DHEA-s level appears to be indicative of MDD severity with respect to depressive symptoms, especially regard-ing guilt and failure. Our findings suggest that the upregulation of DHEA-s may be a part of a compensatory process in very-mild-to-moderate depression, and the failure of this compensation mechanism may underlie the development of severe depression.